Indolent non-Hodgkin lymphomas are a mixed group of hematologic disorders causing significant morbidity in affected patients. As described by the indolent classification, these pathologies are commonly characterized by an elongated natural history, and patients often experience major changes in histological classification over the course of the disease despite having a favorable treatment response.1,2

A review article published in Current Treatment Options in Oncology provided an overview of some common subtypes of indolent lymphomas, including marginal zone, lymphoplasmacytic, and follicular lymphoma. Daniele Grimaldi, MD, of the department of molecular biotechnologies and health sciences at the University of Turin in Italy, and colleagues reviewed the prognostic value of minimal residual disease (MRD) in assessing prognosis and treatment response in patients with these lymphomas.

The researchers also evaluated data regarding the use of MRD detection methods to risk stratify patients, customize therapeutic regimens, and monitor key clinical parameters. Challenges formerly preventing the incorporation of MRD monitoring into everyday practice are now being addressed with the advent of innovative molecular diagnostic techniques such as next generation sequencing and droplet digital polymerase chain reaction (PCR) technologies.

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“Although these techniques are not yet standardized, they will likely increase the reliability and ensure broad applicability of MRD detection in future years,” the reviewers wrote.

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Prognostic Value of MRD: The Positive

The role of MRD as a prognostic marker was first investigated in patients with follicular lymphoma nearly 2 decades ago. Several studies found that standard induction chemotherapy failed to induce molecular remission in malignant B cells. The same group of patients was reassessed 12 years after the initial analysis by a different group of researchers who reported that the majority of the patients were still alive, largely due to the indolent nature of the pathology. These results showed that MRD has individual prognostic value, with clinically meaningful influence on progression-free survival (PFS).

In further prospective phase 3 trials, statistical analysis further confirmed the predictive value of MRD detection in positive and negative clinical outcome determination in relation to PFS, irrespective of the choice of treatment. Similar results were seen in studies assessing long-term disease control. In recent years, MRD status has been integrated into several multicenter, randomized clinical trials as a clinically important measure, and samples are assessed using current molecular biology techniques.

Prognostic Value of MRD: The Negative

The current literature also contains findings that invalidate the predictive value of MRD, specifically in the setting of follicular lymphoma. However, the prognostic failure of MRD described in these studies is largely due to small sample sizes and heterogeneity among the samples evaluated. In addition, several methodological aspects of these studies have been questioned, including the timing of sample collection. These negative studies indicate that although MRD analysis may provide prognostically meaningful indicators, it requires rigorous evaluation before widespread application to clinical settings.